Tumors of the Adrenergic System: Imaging and Therapy

  • Cornelis A. Hoefnagel


The development and subsequent clinical uses of radioiodinated meta-iodobenzylguanidine (MIBG) represent a good example of truly molecular targeting avant la letter. The credit for this goes to Prof. William Beierwaltes, whose group at the University of Michigan in Ann Arbor in the 1960s studied and developed tracers for the adrenal cortex, medulla, and heart. After working with 14C-epinephrine for neuroblastoma (1967) and 14C-dopamine for pheochromocytoma (1973) initially [1], they switched to radioiodinated bretylium analogs and quaternary ammonium derivatives for imaging. Don Wieland synthesized and compared 125I-labelled ortho-, para-, and metaisomers of iodobenzylguanidine and was the first to describe imaging of the dog’s adrenal medulla using 131I-para-iodobenzylguanidine (1980); in 1981, Sisson et al. reported imaging of pheochromocytoma in humans using 131I-MIBG. The downside was that 131I-MIBG was a poor tracer for cardiac imaging and that initial attempts to image other neuroendocrine tumors (NETs) showed false-negative results.


Carcinoid Tumor Objective Response Rate Medullary Thyroid Carcinoma Radionuclide Therapy Islet Cell Tumor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Raffel DM, Wieland DM (2010) Developmento of mIBG as a cardiac innervation imaging agent. J Am Coll Cardiol Img 3:111–116.CrossRefGoogle Scholar
  2. 2.
    Hoefnagel CA, Lewington VJ (2004) MIBG therapy. In: Ell PJ, Gambhir SS (Eds) Nuclear medicine in clinical diagnosis and treatment, 3rd edition. Churchill Livingstone, Edinburgh, pp. 445–457.Google Scholar
  3. 3.
    Hoefnagel CA (1994) Metaiodobenzylguanidine and somatostatin in oncology: role in the management of neural crest tumours. Eur J Nucl Med 21:561–581.PubMedGoogle Scholar
  4. 4.
    Khafagi FA, Shapiro B, Fig LM et al (1989) Labetalol reduces Iodine-131 MIBG uptake by pheochromocytoma and normal tissues. J Nucl Med 30:481–489.PubMedGoogle Scholar
  5. 5.
    Reubi JC (1995) Neuropeptide receptors in health and disease: the molecular basis for in vivo imaging. J Nucl Med 36:1825–1835.PubMedGoogle Scholar
  6. 6.
    Bardiès M, Bardet S, Faivre-Chauvet A et al (1996) Bispecific antibody and Iodine-131-labeled bivalent hapten dosimetry in patients with medullary thyroid or small-cell lung cancer. J Nucl Med 37:1853–1859.PubMedGoogle Scholar
  7. 7.
    Goldsmith SJ (2009) Update on nuclear medicine imaging of neuroendocrine tumors. Future Oncol 5:75–84.PubMedCrossRefGoogle Scholar
  8. 8.
    Troncone L, Rufini V, Montemaggi P et al (1990) The diagnostic and therapeutic utility of radioiodinated metaiodoben-zylguanidine (MIBG). 5 years experience. Eur J Nucl Med 16:325–335.PubMedCrossRefGoogle Scholar
  9. 9.
    Rozovsky K, Koplewitz BZ, Krausz Y et al (2008) Added value of SPECT/CT for correlation of MIBG scintigraphy and diagnostic CT in neuroblastoma and pheochromocytoma. Am J Roentgenol 190:1085–1090.CrossRefGoogle Scholar
  10. 10.
    Wiseman GA, Pacak K, O’Dorisio MS et al (2009) Usefulness of 123I-MIBG scintigraphy in the evaluation of patients with known or suspected primary or metastatic pheochromocytoma or paraganglioma: results from a prospective multicenter trial. J Nucl Med 50:1448–1454.PubMedCrossRefGoogle Scholar
  11. 11.
    Hoefnagel CA, De Kraker J (2004) Pediatric tumors. In: Ell PJ, Gambhir SS (Eds) Nuclear medicine in clinical diagnosis and treatment, 3rd edition. Churchill Livingstone, Edinburgh, pp. 195–206.Google Scholar
  12. 12.
    Leung A, Shapiro B, Hattner R et al (1997) The specificity of radioiodinated MIBG for neural crest tumors in childhood. J Nucl Med 38:1352–1357.PubMedGoogle Scholar
  13. 13.
    Vik TA, Pfluger T, Kadota R et al (2009) (123)I-mIBG scintigraphy in patients with known or suspected neuroblastoma: results from a prospective multicenter trial. Pediatr Blood Cancer 52:784–790.PubMedCrossRefGoogle Scholar
  14. 14.
    Yeh SDJ, Larson SM, Burch L et al (1991) Radioimmunodetection of neuroblastoma with Iodine-131-3F8: correlation with biopsy, Iodine-131-Metaiodobenzylguanidine and standard diagnostic modalities. J Nucl Med 32:769–776.PubMedGoogle Scholar
  15. 15.
    Hoefnagel CA, Rutgers M, Buitenhuis CKM et al (2001) A comparison of targetting neuroblastoma with mIBG and anti L1-CAM antibody mAB chCE7: therapeutic efficacy in a neuroblastoma xenograft model and imaging of neuroblastoma patients. Eur J Nucl Med 28:359–368.CrossRefGoogle Scholar
  16. 16.
    Hoefnagel CA, Delprat CC, Zanin D, van der Schoot JB (1988) New radionuclide tracers for the diagnosis and therapy of medullary thyroid carcinoma. Clin Nucl Med 13:159–165.PubMedCrossRefGoogle Scholar
  17. 17.
    Kauhanen S, Seppänen M, Ovaska J et al (2009) The clinical value of [18F]fluorodihydroxyphenylalanine positron emission tomography in primary diagnosis, staging and restaging of neuroendocrine tumors. Endocr Relat Cancer 16:255–265.PubMedCrossRefGoogle Scholar
  18. 18.
    Koopmans KP, Neels OC, Kema IP et al (2008) Improved staging of patients with carcinoid and islet cell tumors with 18F-dihydroxy-phenyl-alanine and 11C-5-hydroxy-tryptophan positron emission tomography. J Clin Oncol 26:1489–1495.PubMedCrossRefGoogle Scholar
  19. 19.
    Troncone L, Galli G (Eds) (1991) Proceedings International Workshop on the role of [131I]metaiodobenzylguanidine in the treatment of neural crest tumors. J Nucl Biol Med 35:177–362.Google Scholar
  20. 20.
    Baulieu J-L, Guilloteau D, Baulieu F et al (1988) Therapeutic effectiveness of Iodine-131 MIBG metastases of a nonsecreting paraganglioma. J Nucl Med 29:2008–2013PubMedGoogle Scholar
  21. 21.
    Gedik GK, Hoefnagel CA, Bais E, Olmos RA (2008) 131I-MIBG therapy in metastatic phaeochromocytoma and paraganglioma. Eur J Nucl Med Mol Imaging 35: 725–733.PubMedCrossRefGoogle Scholar
  22. 22.
    Safford SD, Coleman RE, Gockerman JP et al (2003) Iodine-131 metaiodobenzylguanidine as an effective treatment for malignant pheochromocytoma and paraganglioma. Surgery 134:956–962.PubMedCrossRefGoogle Scholar
  23. 23.
    Hoefnagel CA (1999) Nuclear medicine therapy of neuroblastoma. Q J Nucl Med 43:336–343.PubMedGoogle Scholar
  24. 24.
    Yanik GA, Levine JE, Matthay KK et al (2002) Pilot study of iodine-131 metaiodobenzylguanidine in combination with myeloablative chemotherapy and autologous stem-cell support for the treatment of neuroblastoma. J Clin Oncol 20:2142–2149.PubMedCrossRefGoogle Scholar
  25. 25.
    Voûte PA, van der Kleij AJ, de Kraker J et al (1995) Clinical experience with radiation enhancement by hyperbaric oxygen in children with recurrent neuroblastoma stage I V. Eur J Cancer 31A:596–600.PubMedCrossRefGoogle Scholar
  26. 26.
    Hoefnagel CA, de Kraker J, Valdés Olmos RA, Voûte PA (1994) 131I-MIBG as a first-line treatment in high-risk neuroblastoma patients. Nucl Med Commun 15:712–717.PubMedCrossRefGoogle Scholar
  27. 27.
    Bleeker G, Schoot RA, Caron HN et al (2013) Toxicity of up-front 131I-metaiodobenzylguanidine (131I-MIBG) therapy in newly diagnosed neuroblastoma patients: a retrospective analysis. Eur J Nucl Med Mol Imaging 40:1711–1717.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Schoot RA, Bleeker G, Caron HB et al (2013) The role of 131I-metaiodobenzylguanidine (MIBG) therapy in unresectable and compromising localized neuroblastoma. Eur J Nucl Med Mol Imaging 40:1516–1522.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Kraeber-Bodéré F, Bardet S, Hoefnagel CA et al (1999) Radioimmunotherapy in medullary thyroid cancer using bispecific antibody and iodine-131-labeled bivalent hapten: Preliminary results of a phase I/II clinical trial. Clin Cancer Res 5:3190s–3198s.PubMedGoogle Scholar
  30. 30.
    Zuetenhorst H, Taal BG, Boot H et al (1999) Long-term palliation in metastatic carcinoid tumours with various applications of Meta-idobenzylgua nidine: pharmacological MIBG, 131I-labeled MIBG and the combination. Eur J Gastroenterol Hepatol 11:1157–1164.PubMedCrossRefGoogle Scholar
  31. 31.
    Safford SD, Coleman RE, Gockerman JP et al (2004) Iodine-131 metaiodobenzylguanidine treatment for metastatic carcinoid. Results in 98 patients. Cancer 101:1987–1993.PubMedCrossRefGoogle Scholar
  32. 32.
    Taal BG, Hoefnagel CA, Valdés Olmos RA et al (1996) Palliative effect of Metaiodobenzylguanidine in metastatic carcinoid tumors. J Clin Oncol 14:1829–1838.PubMedGoogle Scholar
  33. 33.
    Taal BG, Hoefnagel CA, Boot H et al (2000) Improved effect of 131I-MIBG treatment by predosing with non-radiolabeled MIBG in carcinoid patients, and studies in xenografted mice. Ann Oncol 11:1437–1443.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2014

Authors and Affiliations

  • Cornelis A. Hoefnagel
    • 1
  1. 1.Netherlands Cancer InstituteAmsterdamThe Netherlands

Personalised recommendations